Breast Cancer Research This program is focused upon making improvements in breast cancer patient regimens and outcomes, using an interdisciplinary approach. Our program hopes to achieve this goal by utilizing an improved understanding of the distinct biology of the intrinsic subtypes of breast cancer and breast cancer heterogeneity obtained through tissue-based studies, with additional biomarker discovery and validation, risk factor appraisal, and drug development, which lead to new therapeutic trials and population-based studies. Specifically, our strategic goals are: 1) basic and epidemiologic science discovery integrated with our existing understanding of the intrinsic breast cancer subtypes, 2) technological advances in imaging and therapy, 3) mouse models testing of promising therapeutic approaches in models representing the known biological subtypes, and 4) tissue-based discovery and clinical research algorithms for rational drug/combination studies with bidirectional strategies of containing embedded correlative/research biopsy studies. The Breast program is well suited to foster translation of basic science findings Into the clinic and back again because it is heavily integrated into a very active multidisciplinary clinical and clinical-translational operation, n addition, this program is seamlessly integrated with our mature breast cancer SPORE infrastructure that includes clinicians, epidemiologists, and laboratory scientists. Highlights of research by program investigators include development of genetically engineered mouse models representing many of tine intrinsic subtypes allowing subtype-specific therapeutic strategies to be tested in the mouse phase I unit (Perou, Sharpless), the development of anotechnology-based and other novel imaging that can be applied to both small animal and human breast cancers (Zhou, Pisano), and the design and execution of clinical trials using novel regimens and trial designs (Carey, Anders);the clinical focus remains on the manage of subtype-specific prospective clinical trials with targeted agents and embedded correlative analysis of molecular signatures and cross-trial validations. Substantial progress in understanding the risk factors and molecular biology of specific intrinsic subtypes has come from collaborations between faculty from the schools of Medicine, Public Health, and Genetics, including the first identification of the association of basal-like breast cancer with African-American women (Carey, Perou, MiDikan). The population-based Carolina Breast Cancer Study III is integral to this program and is examining subtype-specific risk factors and outcomes with a focus upon African-American women. Complementary studies are examining epigenetic and microenvironmental influences (Troester, Swift-Scanlan) that should address the "soil" contributions to these risks, and a new program in geriatric oncology is focusing upon molecular correlates of breast tumor and host response to therapy (Muss, Sharpless). The Program consists of 24 members from five different schools and clinicians from five different disciplines. In 2009, Breast Research Program members held 56 grants and $12.3M (total cost) in annual extramural funding, including 24 grants and $7.4M (total costs) from the NCI.